Table 4.

CAF modulates cancer progression and drug resistance in different cancers

CAF-mediated cancer progression	Secreted cytokines and chemokines from CAFs	Modulated pathways and signaling in cancer cells	Functions	Resistance to	Cancer types	Ref.
Cancer cell survival	IL-6 CCL5 midkine SDF-1 IGF-1 HGF IL-8 CXCL12 CCL1	STAT3/PI3K/Akt signaling NF-κB pathway JAK2/STAT3 pathway TGF- signaling CXCR4/Wnt/-catenin signaling TGF-β/NF-κB pathway	Proliferation Chemoresistance EMT Cancer cell viability Cell survival	Cisplatin TKI Paclitaxel 5-fluorouracil Paclitaxel Gemcitabine	Ovarian cancer OSCC Lung cancer Breast cancer Pancreatic cancer Colorectal cancer Gastric cancer	[155-163]
CSC modulation	IL-17A TGF-β2 IL-6 IL-8 CD10 and GPR77	Wnt/β-catenin HGF/Met signaling Hh signaling	Self-renewal	Tamoxifen 5-fluorouracil Gefitinib Cetuximab	Breast cancer Colon cancer Melanoma Lung cancer	[44,164-166]
Cancer metabolism	HGF TIGAR	PI3K/Akt GPER/cAMP/PKA/CREB NF-κB NF-κB signaling	Cell survival Tumor progression	TKI Mitoxantrone Paclitaxel Topotecan Tamoxifen	NSCLC	[167-173]
ECM modulation	MMPs Caveolin-1 PDPN	Integrinβ1/PI3K/Akt pathway PI3K/Akt pathways	Tumor progression Tumor invasion	Doxorubicin Tamoxifen TKI	NSCLC Breast cancer PDAC	[86,91,174-182]

CAF: Cancer-associated fibroblast; IL-6: interleukin-6; CCL5: chemokine (CC motif) ligand 5; SDF-1: stromal cell-derived factor 1; IGF-1: insulin-like growth factor-1; HGF: hepatocyte growth factor; IL-8: interleukin 8; CXCL12: chemokine (C-X-C motif) ligand 12; CCL1: chemokine (CC motif) ligand 1; STAT3: signal transducers and activators of transcription 3; PI3K: phosphoinositide 3-kinases; Akt: protein kinase B; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; JAK2: Janus kinase 2; TGF-β: transforming growth factor beta; CXCR4: CXC chemokine receptor type 4; EMT: epithelial-mesenchymal transition; TKI: tyrosine kinase inhibitors; OSCC: oral squamous cell carcinoma; GPR77: G-protein-coupled receptor 77; Hh: hedgehog; TIGAR: TP53-induced glycolysis regulatory phosphatase; GPER: G protein-coupled estrogen receptor; cAMP: cyclic adenosine monophosphate; PKA: protein kinase A; CREB: cAMP response element-binding protein; ECM: extracellular matrix; MMPs: matrix metalloproteinases; PDPN: podoplanin; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma.